The present invention is generally directed toward a surgical bone product and more specifically is a shaped partially demineralized allograft bone device or construct with a mineralized central section.
The use of substitute bone tissue dates back around 1800. Since that time research efforts have been undertaken toward the use of materials which are close to bone in composition to facilitate integration of bone grafts. Development have taken place in the use of grafts of a mineral nature such as corals, hydroxyapatites, ceramics or synthetic materials such as biodegradable polymer materials. Surgical implants should be designed to be biocompatible in order to successfully perform their intended function. Biocompatibility may be defined as the characteristic of an implant acting in such a way as to allow its therapeutic function to be manifested without secondary adverse affects such as toxicity, foreign body reaction or cellular disruption.
Human allograft tissue is widely used in orthopaedic, neuro-, maxiliofacial, podiatric and dental surgery. The tissue is valuable because it is strong, biointegrates in time with the recipient patient""s tissue and can be shaped either by the surgeon to fit the specific surgical defect or shaped commercially in a manufacturing environment. Contrasted to most synthetic absorbable or nonabsorbable polymers or metals, allograft tissue is bioinert and integrates with the surrounding tissues. Allograft bone occurs in two basic forns; cancellous and cortical. Cortical bone is a highly dense structure comprised of triple helix strands of collagen fiber, reinforced with hydroxyapatite. The cortical bone is a compound structure and is the load bearing component of long bones in the human body. The hydroxyapatite component is responsible for the high compressive strength of the bone while the collagen fiber component contributes in part to torsional and tensile strength.
Many devices of varying shapes and forms can be fabricated from allograft cortical tissue by machining and surgical implants such as pins, rods, screws, anchors, plates, intervertebral spacers and the like have been made and used successfully in human surgery. These engineered shapes are used by the surgeon in surgery to restore defects in bone to the bone""s original anatomical shape. This treatment is well known in the art and is commercially available as demineralized bone.
Allograft bone is a logical substitute for autologous bone. It is readily available and precludes the surgical complications and patient morbidity associated with obtaining autologous bone as noted above. Allograft bone is essentially a collagen fiber reinforced hydroxyapatite matrix containing active bone morphogenic proteins (BMP) and can be provided in a sterile form. The demineralized form of allograft bone is naturally both osteoinductive and osteoconductive. The demineralized allograft bone tissue is fully incorporated in the patient""s tissue by a well established biological mechanism. It has been used for many years in bone surgery to fill the osseous defects previously discussed.
Demineralized allograft bone is usually available in a lyophilized or freeze dried and sterile form to provide for extended shelf life. The bone in this form is usually very coarse and dry and is difficult to manipulate by the surgeon. One solution to use such freeze dried bone has been provided in the form of a commercially available product, GRAFTON(copyright), a registered trademark of Osteotech Inc., which is a simple mixture of glycerol and lyophilized, demineralized bone powder of a particle size in the range of 0.1 cm to 1.2 cm as is disclosed in U.S. Pat. No. 5,073,373 issued Dec. 17, 1991 forming a gel. Similarly U.S. Pat. No. 5,290,558 issued Mar. 1, 1994, discloses a flowable demineralized bone powder composition using a osteogenic bone powder with large particle size ranging from about 0.1 to about 1.2 cm. mixed with a low molecular weight polyhydroxy carrier possessing from 2 to about 18 carbons comprising a number of classes of different compounds such as monosaccharides, disaccharides, water dispersible oligosaccharides and polysaccharides.
A recent version of GRAFTON(copyright) product uses relatively large demineralized particles in the carrier to create a heterogenous mixture which provides body or substance to the composition. This material is useful in filling larger defects where some degree of displacement resistance is needed by the filler.
The advantages of using the bone particle sizes as disclosed in the U.S. Pat. Nos. 5,073,373 and 5,290,558 patents previously discussed were compromised by using bone lamellae in the shape of threads or filaments having a median length to median thickness ratio of about 10:1 and higher while still retaining the low molecular weight glycerol carrier. This later prior art is disclosed in U.S. Pat. Nos. 5,314,476 issued May 24, 1994 and U.S. Pat. No.5,507,813 issued Apr. 16, 1996 and the tissue forms described in these patents are known commercially as the GRAFTON(copyright) Putty and Flex, respective.
The combination of natural cortical bone with very desirable mechanical strength and the addition of synthetic (recombinant) BMPs provides a superior form of tissue for surgical use retaining all of the mechanical properties of the cortical component and the accelerated healing offered by the BMP""s.
U.S. Pat. No. 5,972,368 issued on Oct. 26, 1999 discloses the use of cortical contructs (e.g. a cortical dowel for spinal fusion) which are cleaned to remove all of the cellular material, fat, free collagen and non-collagenous protein leaving structural or bound collagen which is associated with bone mineral to form the trabecular struts of bone. It is stated that the natural crystalline structure of bone is maintained without the risk of disease transmission or significant immunogenicity. Thus the shaped bone is processed to remove associated non-collagenous bone proteins while maintaining native bound collagen materials and naturally associated bone minerals. Recombinant BMP-2 is then dripped onto the dowel surface. It could also be added to the cortical bone by soaking in the BMP-2 solution. As noted, this reference teaches the removal of all non-collagenous bone proteins which necessarily include all the naturally occurring BMP""s and relies upon the addition of recombinant BMP-2 in a specific and empirically determined concentration. The naturally occurring BMP""s are present in a concentration unique for each specific BMP protein and has been optimized by nature. The ""368 patent teaches complete removal of the natural BMP""s by demineralization and relies solely on the added rhBMP""s. The surface of a machined cortical bone surface is characterized by a wide variety of openings resulting from exposure by the machining process of the Haversian canals present throughout cortical bone. These canals serve to transport fluids throughout the bone to facilitate the biochemical processes occurring within the bone. They occur at variable angles and depths within the bone. Hence, when the machining occurs, the opening will be varied and unpredictable resulting in a highly variable and uncontrolled amount of BMP entering the surface of the bone.
In WO99/39,757 published Aug. 12, 1999, an osteoimplant is disclosed which uses partially demineralized bone elements and adjacent surface-exposed collagen to form chemical linkages to bond the elements into a solid aggregate. It is noted in the Description of the Preferred Embodiments, that xe2x80x98when prepared from bone derived elements that are xe2x80x9conly superficially demineralizedxe2x80x9d that the osteoimplant will possess a fairly high compression strength approaching that of natural bone. FIG. 2 illustrates bone-derived stacked sheets having a fully or partially demineralized outer surface 21 with surface exposed collagen and a nondemineralized or partially demineralized core 22. As noted in Example 1, the bone sheets approximately 1.5 mm thick were placed in a 0.6N HCl solution for 1.5 hours with constant stirring, washed in water for 5 minutes and soaked for 1.5 hours in phosphate buffered saline. In Example 3 the bone-derived sheets from cortical bone were treated for 10 minutes in 0.6N HCl to expose surface collagen. Bone cubes derived from human cancerous bone were treated to expose surface collagen at the outer borders of the cube. In Example 4, human cortical bone-derived sheets approximately 1 mm thick were surface demineralized for 15 minutes in 0.6N HCl and in Example 5, human cortical bone derived sheets approximately 2 mm thick were surface demineralized for 1 hour in 06N HCl.
U.S. Pat. No. 5,899,939, issued May, 1999, to the same inventor as the foreign patent noted in the paragraph above, discloses a bone derived implant made up of one or more layers of fully mineralized or partially demineralized cortical bone, and optionally one or more layers of some other material. The layers of the implant are assembled into a unitary structure to provide an implant.
In U.S. Pat. No. 5,861,167, issued Jan. 19, 1999, a toothroot is shown to have selective parts of the surface removed by acid to improve subsequent attachment of the tooth in conjunction with periodontal surgery. Similarly U.S. Pat. No. 5,455,041 utilized treatment by demineralizing the tooth root surface with citric acid applied for one minute to effect reattachment of collagen fibers to the root surface and adding growth factors onto the surface of the demineralized root.
Partial demineralization of bone is also disclosed in the Journal of Surgical Research Vol. 59, pages 614-620 (1995) in the article Sterilization of Partially Demineralized Bone Matrix: The Effects of Different Sterilization Techniques on Osteogenetic Properties where particles of bone of 500 microns were treated for 24 hours at 4 degrees C. with 0.6 N HCl with the extent of decalcification determined to be 20% and placed in the bone site. New bone formation was noted after the passage of six weeks.
In French Patent Applications Numbers 2,582,517 and 2,582,518 treatment of fragments of bones taken from animals, primarily cattle were partially demineralized and tanned with glutaraldehyde. The bone elements to be implanted are cut to the desired shape from an ox bone which has been subjected to a treatment comprising a degreasing step with an organic solvent such as ethanol, a demineralization step with a calcium extraction agent such as hydrochloric acid and tanning with glutaraldehyde and subsequent washings. Similar demineralization of bone is shown in U.S. Pat. No. 5,585,116 issued Dec. 17, 1996. This patent also notes that it is known that partial demineralization facilitates integration of a bone graft. This is accordingly followed by different complementary steps which are intended either to deproteinize the bone completely or to act on the nature of the proteins which then remain linked within the bone matrix or else to increase this proportion of proteins.
It is desirable to make the surface of the bone more conductive to receiving BMP""s and other additives without losing the desirable high mechanical strength properties of the cortical bone. It is also desirable to leave most of the naturally occurring protein intact in the bone in such a way as to expose just enough of the bone surface to free the natural BMP""s present on the surface. Since demineralization also reduces the cross sectional area of the bone construct, the bone construct must retain its shape and structural integrity.
Accordingly, the prior art only partially addresses the problems inherent in correcting surgical defects.
The present invention is directed toward the treatment of the surface of cortical bone constructs to modify the surface by removing a layer of the inorganic mineral hydroxyapatite material leaving the mechanical properties of the bone constructs substantially unchanged while providing a surface that allows the addition of BMP""s and other desirable additives to be introduced to the surface and thereby enhance the healing rate of the cortical bone in surgical procedures.
The subject formulation is a demineralized bone structure for application to a bone defect site to promote new bone growth at the site comprising a partially demineralized cortical bone structure, said bone structure comprising a cross sectional surface are ranging from 85% to 95% of the original bone surface area before demineralization with the remaining partially demineralized cortical bone structure comprising an outer demineralized layer ranging in thickness from about 0.05% to about 0.14%. The structure is designed to present the bone matrix and a demineralized surface layer for reception of bone morphogenetic proteins (BMP) and other desired additives. The macrostructure of the highly porous demineralized surface layer serves both as an osteoconductive matrix and to signal the patient""s tissue and cells to initiate the growth of new bone (osteoinduction).
It can be seen that the prior art has attempted to replicate to some degree the present invention by flash demineralization of the surface or full demineralization of the structure.
It is thus an object of the invention to provide a shaped bone implant construct having a partially demineralized cortical bone layer with an interior mineralized bone section to provide compression strength to the implant bone construct.
It is an object of the invention to utilize a partially demineralized shaped bone implant structure to approximate the mechanical strength characteristics of natural bone to provide overall strength and initial durability to the structure.
It is yet another object of the invention to provide a partially demineralized shaped bone implant structure to provide a strong implant structure of a predetermined shape and size for implantation.
It is also an object of the invention to provide a bone derived structure which can effective hold medical and biological composition which promote new bone growth and accelerate healing.
It is an additional object of the invention to use a BMP additive in the demineralized layer of the bone structure.
It is an still additional object of the invention to use a soluble silver additive in the demineralized layer of the bone structure.
It is also an object of the invention to create a bone structure which can be easily handled by the physician.
These and other objects, advantages, and novel features of the present invention will become apparent when considered with the teachings contained in the detailed disclosure which along with the accompanying drawings constitute a part of this specification and illustrate embodiments of the invention which together with the description serve to explain the principles of the invention.